Drug addiction is associated with long-term behavioral changes. Identifying molecules that contribute to these behaviors is an important goal. NAC1 is a member of the POZ/BTB family of transcription factors that demonstrated increases in gene expression weeks after cocaine self-administration in the rat. Manipulation of NAC 1 levels in the rat nucleus accumbens caused changes in cocaine-regulated behaviors, yet the endogenous function of NAC 1 remains unknown. The proposed molecular and behavioral studies are designed to examine the role of NACI in the mammaliml brain and NAC1 's impact on cocaine-induced-behaviors. The specific aims will demonstrate: Aim 1. where NACI is expresseEand how cocaine administration will affect NAC1 's distribution; Immunokigtology will be performed using a polyclonal antibody that detects which cellular nuclei contain NAC 1 and the expression pattern will be determined in those CNS regions known to be involved in cocaine-induced behaviors. Aim 2. what other proteins interact with NAC1; Both POZ-BTB and non-OZ BTB proteins will be examined for their interactions with NAC 1. NAC 1, either full-length or in truncated forms, will be used as the "bait" to screen a mouse brain library, using a yeast two-hybrid screen. The protein-protein interactions will be confirmed by several biochemical tests and each cDNA will be sequenced to determine the identity of the encoded protein. Aim 3. the effects of manipulating NAC1 gene expression? Mice will be bred which do not express NAC1. They will be examined for: their phenotype and the behavioral responses to cocaine. The characterization of NAC 1, a gene that eMaibited long-term changes in expression after cocaine use, will further the understanding of cocaine addiction. The hnman NAC 1 proteinis similar to that of rat and mouse, therefore these experiments may provide important insights into cocaine abuse in humans.